Classic neurological and psychological studies have indicated that memory process consists of learning, consolidation/storage, and retrieval. It is obvious that the present genetic technologies are inadequate for dissecting the role of NMDA receptors in various stages of memory formation. This proposal focuses on a new genetic technology and its application in the study of the molecular mechanisms of memory consolidation. It is hypothesized that the NMDA receptor activity in the hippocampus and/or cortex plays a role in the first two stages: learning and the memory consolidation, but not in memory retrieval. To test this hypothesis, a newly developed gene knockout technology will be employed to produce a mutant mouse in which the loss of NMDA receptor function is inducible, reversible, and subregion- specific. The first major set of experiments will be focused on molecular, biochemical, and electrophysiological characterizations of on these conditional mutants. The second major set of experiments will be conducted to examine whether the sequential activation of NMDA receptors in the hippocampus and/or cortical regions after initial learning is required during the period of memory consolidation. Demonstration of feasibility of new genetic technology should lead to a broad application in dissecting the precise functions of other genes in multiple-processes of various brain functions. Moreover, understanding the molecular mechanisms of memory consolidation and storage may also reveal new strategy for potential therapeutic interventions for the treatment of memory disorders.